Hypertension is a complex disease process involving many pathophysiological changes. In this program Project, the individual research topics focus on the theme that metabolic factors contribute to abnormal blood pressure regulation in hypertension. The strategy of the group is to monitor many relevant variables during the development of hypertension with the goal of defining the complete sequence of events from the introduction of an intervention (experimentally imposed, genetic or clinical_ to the resultant elevation in blood pressure. Among these variables are alterations in neural and endocrine factors, cellular events and molecular and genetic characteristics. Five principal investigators from four departments (three clinical and one basic science) have joined to study these changes. Animal models will include mice, experimental hypertension and transgenically modified), dogs and rats. Additionally, obesity-related hypertension in humans will be evaluated. Among the specific variables measured will be the following: mRNA for specific proteins, enzyme activities, genetic associations, vascular reactivity, blood pressure, hormonal levels, endothelium-derived products and fatty acid levels. Research strategies will utilize the professional expertise and equipment described in two of the three core units (Core B, Animal and Core C, Chemistry). Biostatistics support and scientific management will be coordinated through the Administrative Core (Core A). From these integrated projects, a better understanding of the initiating factors of hypertension will emerge.